The present invention relates to a perfusion circuit for use in delivering substances, such as macromolecular complexes, including small molecules, gene therapy vectors, or the like to the heart.
Cardiovascular disease is a leading cause of death in the United States, and heart failure is a major public health problem in the United States. Gene therapy may provide promising new therapies for this vexing public health problem. However, gene delivery is the most important as yet unsolved problem limiting the applicability of gene therapy for the treatment of heart failure. This applies equally to heart failure due to defined X-linked or autosomal recessive gene defects and to the more common forms of heart failure without a well-defined genetic basis since promising vectors and therapeutic transgenes have been identified for both.
Bridges et al., Annals of Thoracic Surgery, 73:1939-1946 (2002) describe a cardiopulmonary surgical technique for a so-called “incomplete isolation” of a subject's heart in situ. The cardiac isolation technique requires the formation of two separate cardiopulmonary bypass circuits, one for systemic circulation of the body and one for antegrade cardiac circulation of a gene delivery vector. The technique enables multiple passes, or recirculation, of a macromolecular complex through a subject's heart during cardiopulmonary bypass surgery.
A technique which isolates the heart to permit systemic delivery of genes is described in U.S. Provisional Application No. 60/506,367 filed on Sep. 26, 2003 and its corresponding International Application, International Publication No. WO 2005/030292 (Apr. 7, 2005). In addition, a balloon catheter useful in retrograde perfusion of the heart with drugs, gene therapy vectors or other solutions via the coronary sinus is described in U.S. Provisional Application No. 60/504,743 filed on Sep. 19, 2003 and its corresponding International Publication No. WO 2005/027995, published Mar. 31, 2005.
There is need for a perfusion circuit and surgical method that is capable of optimizing drug or gene delivery to the heart in situ during cardiac isolation.